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Serologic Testing for Hepatitis B

Educational Objective
To understand how to interpret the results of diagnostic tests and apply them clinically.
1 Credit CME

A 27-year-old woman without pertinent medical history presented with elevated transaminase levels and a positive hepatitis B surface antigen (HBsAg) test result. Hepatitis B surface antibody (anti-HBs) testing was initially performed 11 months after hepatitis B virus (HBV) vaccination to assess immunologic response before beginning nursing school. Because of elevated liver enzymes and lack of anti-HBs following vaccination, further serologic testing was performed (Table).

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D. The patient has chronic HBV infection.

HBsAg enzyme immunoassay is the first serologic marker to appear in serum at 1 to 10 weeks after infection with HBV and 2 to 8 weeks before the onset of clinical symptoms of hepatitis B.1,2 After acute infection, HBsAg typically disappears 1 to 3 months after symptom onset.1,2 Persistence of HBsAg for more than 6 months, consistent with chronic HBV, is the primary indicator of risk for developing chronic liver disease and hepatocellular carcinoma later in life.1 Thus, HBsAg can assist with diagnosing both acute and chronic hepatitis B.1,2 A negative HBsAg test result rules out acute hepatitis B infection, except during the “window period,” which is the time typically between 100 and 160 days after symptom onset when HBsAg disappears and before anti-HBs appear.1,2 During this time, the total and IgM hepatitis B core antibodies (anti-HBc) are the only serologic markers present.1,2 In the setting of chronic hepatitis B, the absence of HBsAg can occur in the setting of variants in the surface S gene (S-escape variants), evading detection by HBsAg assays and consistent with occult chronic hepatitis B.1,3,4 The prevalence of occult chronic hepatitis B is approximately 0.11% in highly endemic areas.5

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Article Information

Corresponding Author: Maroun M. Sfeir, MD, MPH, MS, Department of Pathology and Laboratory Medicine, Clinical Microbiology Laboratories, University of Connecticut Health Center, Farmington, CT 06053 (sfeir@uchc.edu).

Published Online: November 19, 2021. doi:10.1001/jama.2021.19803

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Hepatitis B. Centers for Disease Control and Prevention. Accessed August 7, 2020. https://www.cdc.gov/hepatitis/hbv/index.htm
2.
Terrault  NA , Lok  ASF , McMahon  BJ ,  et al.  Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance.   Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800PubMedGoogle ScholarCrossref
3.
Raimondo  G , Locarnini  S , Pollicino  T , Levrero  M , Zoulim  F , Lok  AS ; Taormina Workshop on Occult HBV Infection Faculty Members.  Update of the statements on biology and clinical impact of occult hepatitis B virus infection.   J Hepatol. 2019;71(2):397-408. doi:10.1016/j.jhep.2019.03.034PubMedGoogle ScholarCrossref
4.
Makvandi  M .  Update on occult hepatitis B virus infection.   World J Gastroenterol. 2016;22(39):8720-8734. doi:10.3748/wjg.v22.i39.8720PubMedGoogle ScholarCrossref
5.
Yuen  MF , Lee  CK , Wong  DK ,  et al.  Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population.   Gut. 2010;59(10):1389-1393. doi:10.1136/gut.2010.209148PubMedGoogle ScholarCrossref
6.
Clinical laboratory fee schedule. Updated October 1, 2021. Accessed November 15, 2021. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/index
7.
Patel  EU , Thio  CL , Boon  D , Thomas  DL , Tobian  AAR .  Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011-2016.   Clin Infect Dis. 2019;69(4):709-712. doi:10.1093/cid/ciz001PubMedGoogle ScholarCrossref
8.
Amini  A , Varsaneux  O , Kelly  H ,  et al.  Diagnostic accuracy of tests to detect hepatitis B surface antigen: a systematic review of the literature and meta-analysis.   BMC Infect Dis. 2017;17(suppl 1):698. doi:10.1186/s12879-017-2772-3PubMedGoogle ScholarCrossref
9.
Chou  R , Blazina  I , Bougatsos  C ,  et al.  Screening for hepatitis B virus infection in nonpregnant adolescents and adults: a systematic review for the US Preventive Services Task Force.   JAMA. 2020;324(23):2423-2436. PubMedGoogle ScholarCrossref
10.
Guidelines on Hepatitis B and C Testing. World Health Organization; 2017. http://apps.who.int/iris/bitstream/handle/10665/254621/9789241549981-eng.pdf
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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